Prophylaxis with Extended Dosing of BAY94-9027 Decreases Overall and Joint Bleeding Rates with Consistent Consumption for Over 4 Years of Treatment

Objectives: To examine the annualized bleed rate (ABR), joint ABR (JABR) and factor VIII (FVIII) consumption for the main and extension periods of the phase II/III PROTECT VIII trial (NCT01580293), which investigated use of BAY 94-9027, a site-specifically PEGylated recombinant FVIII, for the treatment of hemophilia A.

Methods: In PROTECT VIII, previously treated patients aged 12-65 years with severe (< 1% FVIII) hemophilia A received BAY 94-9027 as prophylaxis or on demand. The three main study dose-frequency groups for prophylaxis were 30-40 IU/kg 2 times a week (2×W), 45-60 IU/kg every 5 days (E5D) or 60 IU/kg every 7 days (E7D). Patients were assigned or randomized to these treatment groups based on their bleeding phenotype; patients completing the main study and entering the extension could switch regimen. Using a cut-off date of 31 January 2018, ABR, JABR, and FVIII consumption were calculated from electronic patient records for the main and extension periods, as were ABR and JABR for the last 12 months in the extension period before data cut-off.

Results: The PROTECT VIII main and extension studies included 110 and 107 prophylaxis patients, respectively, with data available for 85 extension patients on prophylaxis for the last 12 months in the extension. The 107 patients enrolled in both main and extension studies spent approximately 4 years on study since enrollment, with a median (Q1;Q3) of 255 (248;259) days spent in the main study and 1,163 (449; 1579) days in the extension. In prophylaxis patients, median ABR values for the main study, extension, and last 12 months of extension were 2.1, 1.6, and 1.0, respectively; corresponding JABR values were 1.9, 0.9, and 1.0. BAY 94-9027 FVIII consumption was similar for both the main and extension study periods ([Table 1]). Data by treatment regimen are also presented ([Table 1]. Notably, E7D patients had a median ABR and JABR of 0 for the last 12 months of treatment.

Table 1 ABR, JABR and FVIII consumption on prophylaxis in the PROTECT VIII main study^* and extension

Conclusions: In PROTECT VIII, median ABR and JABR in the extension study were lower than those in the main study for patients on prophylaxis treated 2×W, E5D or E7D, with patients who stayed in the E7D group having the lowest ABR and JABR. ABR and JABR for the last 12 months of treatment were generally consistent with values for the whole extension period. FVIII consumption was consistent over time. The results suggest that extended-interval dosing of BAY 94-9027 prophylaxis can maintain low bleed and joint bleed rates, without increasing FVIII dose.

This study was sponsored by Bayer.